Exogenous and endogenous mouse mammary tumor viruses encode superantigen (SAG) in the 3' long terminal repeat. We investigated the immune response of lymph node cells to the viral SAG encoded by endogenous Mtv-2 (vSAG-2) by i.v. injecting splenocytes from Mtv-2+ mice into Mtv-2- congenic counterparts. vSAG-2 stimulation induced blastogenesis and DNA synthesis but not subsequent specific expansion of V beta 14+CD4+ or CD8+ T lymphocytes. Instead, immediate deletion of these T cells progressed after vSAG-2 stimulation, and it was more prominent in both rapidity and degree in CD4+ than CD8+ population and in I-E+ than I-E- mice. vSAG-7 stimulation caused specific expansion of V beta 6+ T cells prior to their deletion as reported. vSAG-7 but not vSAG-2 induced IL-2R expression in the specific T cells. Moreover, the percentage of 5-bromo-2'-deoxyuridine-incorporated cells was about twofold higher in Vbeta6+ T cells stimulated with vSAG-7 than in V beta 14+ T cells stimulated with vSAG-2. The results suggest that vSAG-2 may be a weak mitogen against specific T cells and that T cells weakly activated by SAG may die without preceding expansion. In addition, proliferation of lymphocytes, especially B cells, and enhancement of the expression of IL-2, IL-4, and IFN-gamma messenger RNA were observed. Thus, V beta 14+ T cells stimulated with vSAG-2 were activated to produce cytokines and depleted quickly.